Benzopyrene promotes lung cancer A549 cell migration and invasion through up-regulating cytokine IL8 and chemokines CCL2 and CCL3 expression

Exp Biol Med (Maywood). 2016 Aug;241(14):1516-23. doi: 10.1177/1535370216644530. Epub 2016 Apr 12.

Abstract

Tobacco-sourced carcinogen including benzopyrene (B[a]P) in lung cancer metastasis has not been fully reported. In this study, lung carcinoma A549 cell line was used to investigate the potential roles of tobacco-sourced B[a]P on cell metastasis and invasion and to assess its underlying mechanism. Effects of tobacco-sourced carcinogen on A549 cell proliferation, metastasis, and invasion were analyzed using MTT assay, Transwell assay, and scratch method, respectively. The effects of tobacco-sourced carcinogen on cytokines and chemokines secretion were detected using enzyme-linked immunosorbent assay. Moreover, correlation between inflammatory factor expression and cancer cell migration and invasion was assessed using siRNA-mediated gene silencing. Data showed that both B[a]P and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone either at high or low dose performed no significant difference on A549 cell proliferation with time increasing. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone performed no significant difference on A549 cell migration and invasion while B[a]P significantly increased A549 cell migration and invasion compared to the control group (P < 0.05). Consequently, except for IL-6, IL-8, CCL-2, and CCL-3, secretions were significantly increased by B[a]P treatment compared to the control (P < 0.05). Furthermore, when CCL-2 and CCL-3 were silenced, the migrated and invasive A549 cells were significantly decreased compared to the control, respectively (P < 0.05), while silenced IL-8 drastically decreased the migrated and invasive cells compared to the control (P < 0.01). Taken together, this study illustrated that there may be significant correlation between smoking and lung cancer metastasis. B[a]P maybe an excellent contributor for lung cancer metastasis through up-regulating IL-8, CCL-2, and CCL-3 expression.

Keywords: Lung cancer; cell invasion; cell migration; chemokine CCL-2 and CCL-3; cytokine IL-8.

MeSH terms

  • A549 Cells
  • Benzopyrenes / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism*
  • Chemokine CCL3 / genetics
  • Chemokine CCL3 / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism*
  • Neoplasm Invasiveness*
  • Neoplasm Metastasis
  • Nitrosamines / pharmacology*
  • RNA Interference
  • Tobacco Products
  • Up-Regulation

Substances

  • Benzopyrenes
  • CCL2 protein, human
  • CCL3 protein, human
  • CXCL8 protein, human
  • Chemokine CCL2
  • Chemokine CCL3
  • Interleukin-8
  • Nitrosamines